Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling.
Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling.
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人参皂苷 Rg1 通过 Nrf2/HDAC2 信号传导减弱角质形成细胞中紫外线 B 诱导的糖皮质激素耐药性
DOI：
10.1038/srep39336
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发表时间：
2016-12-16
影响因子：
4.6
通讯作者：
Ling C
中科院分区：
文献类型：
--
作者：
Li J;Liu D;Wu J;Zhang D;Cheng B;Zhang Y;Yin Z;Wang Y;Du J;Ling C
紫外线(UV)照射后发生的氧化应激通常会导致糖皮质激素(GC)抵抗和随后的皮肤炎症。保护皮肤免受紫外线辐射的一种方法是使用抗氧化剂。人参皂苷Rg1是从药用植物人参中分离得到的一种新型天然抗氧化剂。我们发现，UVB暴露会加剧炎症，降低人角质形成细胞(HaCaT细胞)糖皮质激素受体(GR)水平和地塞米松(Dex)的疗效。Rg1可增加UVB照射后HaCaT细胞GR的表达，恢复Dex对炎症反应的反应性。从机制上讲，Rg1挽救了UVB诱导的HDAC2降解。HDAC2基因敲除可部分阻断Rg1诱导的GR上调和GC敏感性增强。此外，Rg1减少了在HDAC2上调之前的ROS的产生，从而使细胞对地塞米松敏感。此外，Rg1处理促进了Nrf2的易位和激活。NRF2基因敲除可部分阻断Rg1诱导的ROS产生减少和HDAC2增加。Rg1还增强了地塞米松对UVB照射小鼠皮肤的抗炎作用。综上所述，我们证明了Rg1减弱了UVB诱导的GC不敏感性。值得注意的是，这些效应部分是由Nrf2/HDAC2途径介导的。
Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plantPanax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells). Pretreatment with Rg1 increased the expression of GR and restored Dex responsiveness to inflammation in UVB-irradiated HaCaT cells. Mechanistically, Rg1 rescued UVB-induced HDAC2 degradation. HDAC2 knockdown partially abolished the Rg1-induced up-regulation of GR and the enhancement of GC sensitivity. In addition, Rg1 reduced the production of reactive oxygen species (ROS), which preceded the up-regulation of HDAC2, and consequent sensitization of cells to Dex. Moreover, Rg1 treatment promoted the translocation and activation of Nrf2. Nrf2 knockdown partially abolished the Rg1-induced decrease of ROS production and increase of HDAC2. Rg1 also potentiated the anti-inflammatory effects of Dex in UVB-irradiated mouse skin. In conclusion, we demonstrated that Rg1 attenuated UVB-induced GC insensitivity. Notably, these effects were partially mediated by the Nrf2/HDAC2 pathway.
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影响因子：
14.9
作者：
Malhotra D;Portales-Casamar E;Singh A;Srivastava S;Arenillas D;Happel C;Shyr C;Wakabayashi N;Kensler TW;Wasserman WW;Biswal S
通讯作者：
Biswal S
组蛋白脱乙酰基酶2介导的糖皮质激素受体的脱乙酰基化可以抑制NF-kappab。
影响因子：
15.3
作者：
Ito, Kazuhiro;Yamamura, Satoshi;Essilfie-Quaye, Sarah;Cosio, Borja;Ito, Misako;Barnes, Peter J;Adcock, Ian M
通讯作者：
Adcock, Ian M
影响因子：
5.9
作者：
Kim HK
通讯作者：
Kim HK
DOI：
10.1159/000064535
发表时间：
2002-09-01
期刊：
SKIN PHARMACOLOGY AND APPLIED SKIN PHYSIOLOGY
影响因子：
--
作者：
de Gruijl, FR
通讯作者：
de Gruijl, FR
DOI：
10.3736/jcim201090410
发表时间：
2010-04-01
期刊：
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine
影响因子：
--
作者：
Jia, Lin;Wang, Wan-yin;Li, Min
通讯作者：
Li, Min